Device and cover providing access to samples in a sample plate

ABSTRACT

A device formed of a sampling “plate” includes an assembly of elements for individual storage samples regularly arranged in a line x column matrix, each of the storage elements may be accessed for placing or taking a sample, a lid may be installed on the plate in order to isolate the storage elements from the environment. The lid includes movable access elements enabling, in a first opening position, to access at least one of the storage elements and, in a second closing position, to isolate the at least one of the storage elements from the environment in order to enable, in the first opening position, access to the one storage elements the lid being arranged on the plate and including one fixed part and at least one mobile part. The mobile part is a disk mobile in rotation or a plate in translation.

The present invention relates to a sampling plate device with a lidenabling access to the samples. It finds application in the field ofsample handling and, in particular, automated placing and takingbiological products. A lid for a sampling plate is also included in theinvention.

Modern sample analysis means make use of <<plates >> which are trays,generally made of thermoplastic or thermosettable synthetic material,comprising an assembly of means for individual storages of samples.These storage means are of cup, well or tube type wherein the samplesare arranged individually. The terms cups, well and tubes are consideredas functionally equivalent within the framework of the invention and arealso grouped under the designation ‘storage means’. These storage meansare generally arranged on the <<plate>> according to a regulardistribution, in a line x column matrix.

Conventionally, <<plates>> including 96 storage means are available andit is possible to access each storage means individually as well toinsert a sample therein, take a sample or perform any operationnecessary within the framework of an analysis. Access to a sample isprovided without any contamination of the other samples. The term samplerefers to any product or composition which may be inserted in thestorage means, for example a product to be analysed or a reactiveproduct. For example, the samples may correspond to an increasingdilution of the same product and the analysis may consist in insertingdifferent reactants according to the storage means considered or thesame reactant in several storage means, as well within the framework ofa qualitative analysis as a quantitative analysis.

Outside the time periods where it is necessary to access the storagemeans, it is generally necessary to close hermetically each of thestorage means to avoid contamination of or to the environment, possiblyamong the storage means or evaporation of the samples. It may be forexample necessary to stir the <<plate>> in order to mix several productsforming the sample and it goes without saying that preferably thestorage means should then be closed.

At the moment, the closing of the <<plates>> is provided by a removablelid which is withdrawn or replaced by the user each time he needs toaccess one or several of the samples. For usages such as PCR, differenttypes of lids and of <<plates>> are thus offered on the market:continuous lid exhibiting under the lower portion studs for insertioninto the well or <<plates>> integrating strips of eight tubes whereon issuperimposed an eight-plug strip. More recently, to comply with theautomation need, companies have developed machines for ensuring theclosing of the <<plates>>: an automaton screwing plugs one by one orautomata capable of sealing on a <<plate>> a plastic film fed by anunwinder roll. Once the lid in place, the samples are therefore notaccessible any longer and the lid must be removed in order to accessthereto.

These diverse techniques may exhibit shortcomings and, for example, thelid may possibly strongly resist the opening and there is then a risk oftoppling the samples in case of sudden release. Moreover, access to thesamples is made in an all or nothing pattern, i.e. an assembly ofstorage means which becomes accessible once the lid has been removedwhereas only a small number of samples may be required in this set. Onethus incurs the risk of contaminating samples to which there is no needto access.

It may therefore be particularly useful to have an individual or persub-assembly or global access means, of storage means of a sampling<<plate>> which does not involve removing a lid.

It is thus that since the documents GB-2 356 253 or EP-10 25 902 or WO01/51099, sliding aperture devices have been known, enabling to mask orto expose reservoirs.

Below, the term <<plate >> will be used in quotes to designate theelement including the storage means and to differentiate it from theword plate in its meaning as a thin elongated element and whichcorresponds to the general shape of the <<plate>> and of certain meansof the invention as will now be seen.

There is therefore provided a device formed of a sampling “plate”comprising an assembly of means for individual storage samples regularlyarranged in a line x column matrix, whereas each of the storage meansmay be accessed for placing or taking a sample, a lid may be installedon the <<plate >> in order to isolate the storage means from theenvironment.

According to the invention, the lid comprises movable access meansenabling, in a first opening position, to access at least one of thestorage means and, in a second closing position, to isolate said atleast one of the storage means from the environment in order to enable,in the first opening position, access to said at least one storage meanswhereas the lid is arranged on the <<plate>>.

In diverse embodiments of the invention, the following means liable tobe combined according to all the technically available possibilities areemployed:

-   -   the storage means are regularly arranged in a line x column        matrix,    -   the gauge of the matrix is square, rectangular, triangular,        polygonal, oval or circular, (signifies that the outermost        storage means of the <<plate>> are on this type of curve)    -   the device comprises a number N of storage means, N being        greater than or equal to 16,    -   the lid comprises one fixed part and at least one mobile part,        the parts being superimposed,    -   the lid comprises one fixed part and at least one mobile part,        said parts being superimposed, and the fixed part is a plate        arranged against the <<plate>> spanning storage means, the plate        comprising at least one access port per storage means, and the        mobile parts each include at least one aperture,    -   the mobile parts include at least one aperture per corresponding        access port,    -   the lid comprises one fixed part and at least one mobile part,        said parts being superimposed, and the mobile parts are arranged        against the <<plate >> spanning at least one storage means and        the fixed part comprising at least one access port per storage        means spans the assembly composed of <<plate>> and mobile part,        and the mobile part(s) comprise at least one aperture,    -   the mobile part(s) comprise at least one aperture per        corresponding access port,    -   the mobile part may be moved relative to the fixed part for at        least one storage means, so that in the first opening position,        the aperture coincides with the corresponding port and that, in        the second closing position, the aperture does not coincide with        a corresponding port,    -   a slit cover is moreover arranged over the assembly composed of        the fixed and mobile part(s),    -   a slit cover is moreover arranged over the mobile part(s),    -   the displacement corresponds to a translation,    -   the displacement corresponds to a rotation,    -   the storage means are cups,    -   the storage means are wells,    -   the storage means are tubes,    -   the fixed part includes one port of predetermined shape per        storage means and the mobile part includes one aperture of the        same predetermined shape, whereas the edges of the port and of        the aperture coinciding substantially in the first opening        position,    -   the lid is removable on the <<plate >>,    -   the lid is interconnected with the <<plate >>,    -   in the case of a lid including several mobile parts, at least        two mobile parts include therebetween at least one reciprocal        driving means,    -   the driving means between two or more mobile parts is        disengageable,    -   the fixed part and the mobile part are superimposed plates which        may translate relative to one another,    -   the translation comprises at least one sliding means        (guillotine),    -   at least one mobile part of the lid controls access to at least        one line or column of corresponding storage means,    -   one mobile part in translation controls access to at least one        line or column of storage means,    -   the lid comprises one mobile part in translation for all the        storage means,    -   as a driving means, at least two mobile parts in translation are        anchored to a detachable rigid linking part, said linking part        enabling the transmission of the translation between the mobile        parts anchored to one another,    -   the linking part is a rod covering mobile parts, and may slide        on the mobile parts which are not anchored to one another, (the        linking part runs as a rolling bridge on the non-anchored mobile        parts),    -   the mobile part is a disk mobile in rotation with respect to the        fixed part, the fixed part being a plate and the disk having a        circular periphery,    -   the lid comprises one disk per storage means,    -   the lid comprises at least one disk common to a sub-assembly of        storage means adjacent to one another,    -   the sub-assembly comprises a number S² of adjacent storage means        forming a square matrix with S>1 and, more preferably with S=2        for a sub-assembly of four storage means,    -   the lid comprises at least one disk common to a sub-assembly of        storage means adjacent to one another, the sub-assembly        comprises a number S² of adjacent storage means forming a square        matrix with S>1 and, preferably with S an even number, and more        preferably with S=2 to control access to a sub-assembly of four        storage means,    -   as a driving means, the disks comprise at their peripheries        teeth on at least one sector, said teeth of two adjacent disks        engaging into one another to form the reciprocal driving means.

The invention also relates to a lid according to the one or several ofthe essentially combined, corresponding preceding characteristics.

This device exhibits several advantages:

-   -   (i) It is cheap and does not require any costly equipment.

(ii) It does not require any significant effort on the user's part forthe operation thereof. Access to the storage means may be provided in asingle operation, by simple sliding of approximately 5 mm or by arotation according as the case may be, the assembly of the well (or a orseveral sub-assemblies) being then open or closed according to theposition.

-   -   (iii) Contrary to the existing systems, the device of the        invention prevents any contamination of the samples in a given        well by those of the adjacent wells.    -   (iv) It is adaptable to automation.    -   (v) Its integrity is preserved during the manipulations, which        is not the case of the systems using plug strips or a film.    -   (vi) It may be made of sterilisable materials and consequently        may be re-usable. It may also be of throw-away type, thanks to a        cheap realisation.    -   (vii) According to the materials, it may resist a wide        temperature range (required for PCR) and storage at −20° C. or        80° C.

The invention will now be exemplified by the detailed description of twoembodiments and in connection with:

FIG. 1 representing a 96-well plate,

FIG. 2 representing a fixed part of a first type of lid,

FIG. 3 representing a superimposition <<plate>> and fixed part,

FIG. 4 representing mobile parts in rotation against one fixed part,

FIG. 5 representing a detailed view of a rotational driving system ofmobile parts,

FIG. 6 representing a second slit, fixed part, so-called cover of thelid,

FIG. 7 representing an exploded perspective view of the <<plate>>, ofthe fixed and rotational mobile parts and of the cover,

FIG. 8 representing a part of a second type of lid,

FIG. 9 representing one mobile part of the second type of lid in openposition,

FIG. 10 representing one mobile part of the second type of lid in closedposition after sliding,

FIG. 11 representing a perspective view of a fixed part intended forinsertion into a <<plate>>.

The device is formed of a <<plate>> with storage means of the cup, wellor tube type, covered with a lid which may be detachable or not, i.e. itmay be removed if necessary or it is fixed permanently. The lid iscomposed of two (or more) superimposed parts in the form of plates whichwill be positioned on the <<plate>>. The first part is fixed and isdrilled at regular intervals with access ports in relation with thestorage means of the <<plate>>. Preferably, the fixed part integrates inits lower section, studs engaging into the wells or the tubes of a wellor tube type <<plate>> for ensured tightness of the assembly coveringthe fixed part on the <<plate>>. The second part(s) are, conversely,mobile in translation (guillotine) or rotation with respect to the fixedpart in order to expose or not the storage means by coinciding or notthe ports of fixed part and apertures of mobile part(s). Thedisplacement of the fixed and mobile parts relative to one anothercorresponds therefore to a translation (or slide) which may be eitherlinear or rotational.

The structure of the second part(s) depends on the embodiment of theinvention and two options are possible and for example in function of amanual or robotised usage.

In a first option, the second part is mobile in rotation on the fixedpart. In the case of a <<plate >> fitted with 96 wells or tubes, 24notched disks are arranged on the fixed part, each covering the surfaceof four wells or tubes. The second part in the form of a disk is drilledby apertures so that during rotation, the apertures will be superimposedwith respect to the ports of the first plate. In the case of notcheddisks for common driving of the assembly or of a sub-assembly of thedisks, one or several disks integrate in their centres a nest wherein isinserted a rod whereof the end matches the nest for rotational driving.Preferably, all the disks are identical and include said nest, thedriving of the disks may then be controlled from any disk. Thus, asimple rotation of that rod will induce a movement of the disk whereofthe notches will ensure the rotation of the others, like a snowballeffect. A cover may span the mobile parts, the latter being thensandwiched between the fixed part and the cover. In an alternative, themobile parts are against the <<plate>>.

In a second option, the second part with apertures is mobile intranslation on the first part for masking or exposing correspondingports and hence provides access or not to the storage means. Severalmobile parts in translation may be arranged on the fixed part, each forone or several lines and/or columns.

A slit cover may therefore be arranged over the mobile part(s) to holdthem in place, whereas they are free in rotation. It is obvious that thecover is slit to provide access to the storage means when the mobilepart is in opening position. Alternately, the mobile part(s) is (are)arranged against the <<plate >> and the fixed part covers the assemblycomposed of the mobile part(s) and <<plate>>, the fixed part thenplaying also the part of the cover of the previous embodiment whilelimiting the number of elements necessary.

In the first as well as in the second option, the number of storagemeans corresponding to a given mobile part may be included between one(one mobile part per storage means) and the number total of storagemeans (one single part in translation on the fixed part or a single diskin the case of a circular gauge matrix of storage means on the <<plate>>).

On FIG. 1, a <<plate >>1 fitted with 96 wells 2 is seen from above. Thewells are arranged according to a regular rectangular line/columnmatrix. The plate is made in a sheet of rigid material and, preferably,in a hot-moulding synthetic material. Alternately, the plate is a thicksheet of rigid material and the wells are provided in said thickness.Within the framework of the invention, the tubes may be detachable ornot and, in the latter case, the lid exhibits the additional advantageof being able to lock in place, on the <<plate>>, the detachable tubes.

On FIG. 2, the fixed part 3 of a first type of lid (first option) isseen from above. This part is realised in a sheet of rigid material and,preferably, in a hot-moulding synthetic material. The fixed part isintended for application over >>the plate>> as represented on FIG. 3 andit comprises access ports 4 enabling to access to the wells. This fixedpart is generally flat in shape.

FIG. 3 enables to visualise the assembly composed of the <<plate>> 1 andthe fixed part 3. The wells 2 are visible by transparency as dottedlines and it may be noticed that the access ports 4 are arranged tocoincide With the wells.

FIG. 4 represents several mobile parts which in this first type of lidare circular disks 5, mobile in rotation around an axis running throughthe centre of the disk. Each of the disks comprises four apertures 6.Each disk 5 is hence in relation with a sub-assembly of four storagemeans 2 in square matrix relation of the <<plate>>. The rotational axisof the disk runs substantially through the centre of the matrix so thata rotation of the disk causes either the masking of the access ports 4or the exposure of said ports. On FIG. 4 the access ports of the fixedpart are masked by the disks and said ports 4 and the storage means 2have been represented in transparency. As explained below, the disks aredriven together into rotation thanks to the rotation of the key-operatedcontrol member 7 whereof the key 8 is represented on the left on FIG. 4.In order to hold the disks axially, corresponding pins and bearings areprovided between the fixed part and the disk. Other means (mobile partsandwiched between <<plate>> and fixed part or between cover and fixedpart) explained below are also usable in combination or not with thepins and the bearings.

The control member 7 is included in one or several disks at the centrethereof. It is possible according to the distribution of the notchessituated at the periphery of the disks to open or close, by simplerotation, a sub-assembly or the assembly of the storage means. Thedifferent distributions of the notches will correspond to distinctversions of the product (such as for example on FIG. 5). The key 8 ismore particularly intended for manual control. It is contemplated to usea key-operated member on a machine for automated opening and closing ofthe access to the storage means.

FIG. 5 details the collective driving notch mechanism of the disks 5thanks to teeth 9 engaging into one another between adjacent disks. Theteeth 9 may be spread over the whole circumference of the disk 5 or,preferably on four sections only (or fewer) in order to limit thepossibility of rotation between both closing and opening positions. Anactive rotation-limiting means may also be implemented by one or severallocking teeth or an abutting toe. It is also possible to definesub-groups of disks in common rotation in order to grant access only tothe storage means of the corresponding sub-group by providing disks withfewer than four toothed sections. Detachable driving means (clutch)between two or more sub-groups are usable.

This first option wherein the mobile parts are disks, is not intendedfor limiting the invention and other sizes of disks, other shapes andnumbers of ports and apertures are contemplated than those represented,de-coupling (re-coupling—engaging) of the collective driving in severalindependent sub-group may also be implemented. The disk may be ofdifferent size according to the embodiment between one disk per storagemeans or one disk for all. In practice, one uses a disk for S² storagemeans grouped in a sub-assembly according to a square matrix with S>1,i.e. 4, 9, 16 or more storage means. It is however preferable that thenumber of storage means of the sub-assembly accessed by a disk is aneven number so that the rotational axis does not coincide with one ofthe storage means. However, the greater the number of storage means perdisk, the more complex the shape and arrangement of the ports and oneprefers the disk for one or, as represented, for four storage means.

Finally, in particular in case when several well correspond to the samedisk, more than two positions may be obtained, for example intermediatepositions where only some of the wells are accessible in thesub-assembly.

FIG. 6 is a top view of a fixed cover 10 which is slit by apertures 11which are superimposed on the apertures of the fixed part. At least onecircular drilling of the fixed part 10 enables access to the controlmember 7 of one of the disks. The fixed part 10 is interconnected to thefixed part 3 by sealing screws or tabs 12.

In this configuration, the disks are sandwiched between the fixed partin contact with the <<plate>> and the cover as represented on FIG. 7.

FIG. 7 is an exploded perspective view of the fixed 3 and mobile 5 partsand of the cover 10. The fixed part 3 includes in its lower section 96empty honeycombs 13 which enable the nesting thereof on the <<plate>>1fitted with 96 wells 2. The cover 10 is preferably emptied in its innersection at the contact with the disks to enable the rotation thereof inthe thickness of the cover thereby holding them axially. The disks aretherefore housed in the thickness of the cover.

FIG. 8 is a top view of one fixed part 14 for a second type of lid(second option). The fixed part 14 comprises half-moon access ports 15which coincide with the storage means 2 visible in transparency on theone hand and directly on the other hand by the access ports 15. Aspreviously, the fixed part 14 is arranged on the <<plate>>, coveringsaid plate. The fixed part 14 exhibits girders 16 on its length,enabling the sliding of one mobile part 17 (FIG. 9). Alternately, themobile part(s) is (are) arranged on <<the plate>> as explained at alater stage.

FIG. 9 enables to visualise apertures 18 regularly arranged on onemobile part 17 in translation. The mobile part 17 may be moved intranslation on the fixed part thanks to the girders 16 enabling thesliding of the mobile part 17 whereof the translation is guided by toes19. On FIG. 9, the ports and the apertures do not coincide and thestorage means are not accessible.

FIG. 10, the mobile part 17 of the lid corresponding to FIG. 9 has beenmoved by sliding on the fixed part 14 and the ports are coincided withthe apertures 18, rendering accessible the storage means of the<<plate>>.

FIG. 11 provides a perspective view of the second type of lid whereinthe fixed part 14 comprises cylindrical extensions 20 (or honeycombs ofthe same type as those 13 of FIG. 7) intended for insertion in the wellto ensure tightness between the plate and the fixed part 14. Asrepresented on FIGS. 7 and 11, the lid in both options includes in itslower section 96 emptied honeycombs which enable the insertion thereofon the plate fitted with 96 wells, rendering the assembly perfectlyhermetic. It is obvious that in such a case, the mobile part(s), in casewhere each of them gives access to several storage means, may not bearranged directly on the <<plate >>.

The invention is not limited by the previous description of the devicefitted with sliding mobile parts or the rotational device and othershapes and numbers of ports and/or apertures are contemplated for thelid. Besides, the sliding mobile part may have a more limited surfacearea to correspond to a particular sub-assembly of storage means, forexample, one, two or more lines or columns. In case when several slidingmobile parts are implemented, a collective driving, disengageable ornot, may be applied.

1-10. (canceled)
 11. A device formed of a sampling <<plate >> (1)comprising an assembly of means (2) for individual storage of samples,whereas each of the storage means may be accessed for placing or takinga sample, whereas a lid may be installed on the <<plate >> in order toisolate the storage means from the environment, the lid includingrotational movable access means (3, 4, 5, 6, 10) enabling, in a firstopening position, to access at least one of the storage means and in asecond closing position to isolate said at least one of the storagemeans from the environment in order to enable, in the first openingposition, access to said at least one storage means whereas the lid isarranged on the <<plate >>, characterised in that the storage means areregularly arranged in a line x column matrix and that the lid comprisesone fixed part (3, 10) and at least one mobile part (5), said partsbeing superimposed, and in that the fixed part is a plate comprising atleast one access port (4) per storage means, and in that the mobileparts are circular periphery disks, mobile in rotation and comprising atleast one aperture (6) per corresponding access port, whereas the diskmay be moved relative to the fixed part for at least one storage means,so that, in the first opening position, the aperture coincides with thecorresponding port and that, in the second closing position, theaperture does not coincide with the corresponding port.
 12. A deviceaccording to claim 11, characterised in that the plate is arrangedagainst the <<plate >> spanning storage means.
 13. A device according toclaim 11 characterised in that the disks are arranged against the<<plate >> spanning at least one storage means.
 14. A device accordingto claim 1, 2 or 3, characterised in that it includes moreover a slitcover (10) spanning the assembly composed of the fixed and mobilepart(s).
 15. A device according to claim 11, characterised in that inthe case of a lid including several disks, the disks includetherebetween at least one reciprocal driving means (7, 9).
 16. A deviceaccording to the claim 15 characterised in that, as a driving means, thedisks comprise at their peripheries teeth (9) on at least one sector,said teeth of two adjacent disks engaging into one another to form thereciprocal driving means.
 17. A device according to the claim 15,characterised in that at least one of the disks comprises a centralnest-type control member (7) intended for receiving a rotational drivingkey (8).
 18. A device according to the claim 15, characterised in thatat least one disk comprises an active rotation-limiting means with alocking tooth or an abutting toe.
 19. A device according to claim 11characterised in that the lid comprises at least one disk common to asub-assembly of storage means adjacent to one another, the sub-assemblycomprises a number S² of adjacent storage means forming a square matrixwith S>1 and, preferably with S an even number, and more preferably withS=2 to control access to a sub-assembly of four storage means.
 20. A lidfor sampling “plate”, the sampling “plate” comprising an assembly ofmeans for individual storage of samples, whereas each of the storagemeans may be accessed for placing or taking a sample, whereas the lidmay be installed on the <<plate >> in order to isolate the storage meansfrom the environment, the lid including rotational movable access means(3, 4, 5, 6, 10), enabling, in a first opening position, to access atleast one of the storage means and, in a second closing position, toisolate said at least one of the storage means from the environment inorder to enable, in the first opening position, access to said at leastone storage means whereas the lid is arranged on the <<plate>>,characterised in that the storage means are regularly arranged in a linex column matrix and that the detachable access means of the lid compriseat least one disk mobile in rotation, the combination of the lid and ofthe <<plate >> forming a device according to any of the precedingclaims.